UF Health research points to potential treatment for macular degeneration, uveitis

Inflammation is a major culprit in age-related macular degeneration and some other eye diseases. Now, University of Florida Health researchers have found a promising treatment that inhibits those diseases by interrupting the process that causes inflammation at its earliest steps.

After testing it in a mouse model, researchers believe the treatment could ultimately be used for various inflammatory eye diseases in humans. The approach uses an inhibitor protein derived from a virus to disrupt inflammation, which plays a role in the progression of one form of age-related macular degeneration. Their findings were published in the January edition of the journal Human Gene Therapy.

The researchers’ discovery could be significant for those who suffer from the “dry” form of macular degeneration, a disease of the retina that causes blurry central vision and sometimes leads to blindness. An estimated 12 million people in the United States have dry macular degeneration.

They also found that the therapy is effective on uveitis, an eye inflammation that affects some 40,000 people each year. Currently, there is no effective treatment for dry macular degeneration. Long-term use of steroids to treat eye inflammations such as uveitis increases the risk of glaucoma.

The researchers used an adeno-associated viral vector to deliver an inflammation-blocking protein into the eye. Their approach involves plucking the gene that makes the beneficial protein from a myxoma virus, typically found in rabbits in Australia and parts of Europe, and inserting it into the AAV vector. The modified AAV vector inhibits the immune response that causes inflammation in diseased eye tissues, according to the study’s findings. The therapy was first tested in tissue cultures and then the mouse model.

“The idea of taking an inflammation inhibitor from a virus and coupling it with gene therapy is novel,” said Grant McFadden, Ph.D., a professor in the department of molecular genetics and microbiology in the UF College of Medicine who collaborated with other UF Health researchers.

Stopping such inflammation in diseased tissues is crucial, McFadden said.

“When you can’t shut inflammation off, you’re faced with chronic or killing diseases,” he said.The new therapy is appealing because of a unique characteristic that allows a single treatment to remain in the eye for the lifetime of the patient. Currently, uveitis is treated with a regimen of eye drops or pills that contain a corticosteroid.

While the treatment is injected behind the lens to the cells lining the back of the eye, McFadden called it the genetic version of a long-acting, slow-release capsule.

“Our approach would be ideal because the therapy could last a significant amount of time in the eye,” said Cristhian Ildefonso, Ph.D., a postdoctoral associate in the department of molecular genetics and microbiology who was the lead author of the journal article.

If AAV vectors can help deliver the anti-inflammatory genes to a damaged or diseased part of the body, researchers believe that the treatment could be used on a host of other conditions, including gout, osteoarthritis, rheumatoid arthritis and bowel diseases, McFadden said. They even see a potential use in fighting vascular problems such as atherosclerosis, which hardens arteries.

“There’s probably not a single organ or tissue that is not susceptible to inflammation,” McFadden said. “We hope this is just the start of being able to exploit it for other inflammatory diseases.”

McFadden collaborated on the research with Alfred S. Lewin, Ph.D, a professor in the department of molecular genetics and microbiology who holds the Shaler Richardson Chair of Ophthalmic Science. Among the other UF Health researchers working on the project was Masmudur Rahman, Ph.D., a research assistant professor in the department of molecular genetics and microbiology.

Lewin said he is encouraged by the therapy’s long-lasting effects and its potential for treating diabetic retinopathy, a major cause of blindness in working-age people.

“It would be difficult to keep giving a drug over and over,” Lewin said. “That’s why we focused on gene therapy.”

Additional studies are needed before the therapy will be tested in people, McFadden said.

The study was funded by grants from the National Eye Institute, which contributed $750,000 over three years; the National Institute of Allergy and Infectious Diseases; the Macula Vision Research Foundation and the Florida Biomedical Research Foundation.